This Is MS Multiple Sclerosis Knowledge & Support Community

we've been over the whole range thing plenty, even within this topic alone. the 'normal' ranges are far too wide. and the choice of units can make things even more problematic. however you slice it, deficiency is found within the normal ranges for both zinc and magnesium. if the observer is zoomed out too far, they just need to use more decimal places. more: http://www.thisisms.com/forum/regimens- ... c2489.html (scroll to bloodwork section)

more about the enzymes required for a functioning d3 pathway:

Vitamin D biosynthesis and its disorders (2002)
"There appear to be active but distinct 25-hydroxylases in both the endoplasmic reticulum and the mitochondria, although the mitochondrial enzyme (P450c25, also known as CYP27A1) appears to be the physiologically more important."

zeroing in on CY P450C25... there are limited google scholar results on this beastie AS P450C25 (over half of the 20 or so studies within the last decade).. i will need to spend more time on the results for CYP27A1 to see what i can tease out this time.

sticking with P450C25 for now, here's one tidbit often mentioned in the few studies i found so far:

Rickets and osteomalacia (2009)
"Vitamin D is hydroxylated in hepatocyte mitochondria by the enzyme P450c25, forming the 25-hydroxyvitamin D metabolite, which is also called calcidiol."

adding the search term 'zinc' takes my results down to five studies, and all the keyword hits are on zinc fingers. so, we'll just have to be patient, or get busy filling this research gap.

will move on to cyp27 now... i know i already looked at this connection so will probably just link back to existing posts in my regimens thread.

jimmylegs wrote:Vitamin D biosynthesis and its disorders (2002)
"There appear to be active but distinct 25-hydroxylases in both the endoplasmic reticulum and the mitochondria, although the mitochondrial enzyme (P450c25, also known as CYP27A1) appears to be the physiologically more important."

Vitamin D is somewhat unique in that metabolism can occur in the cells as well as in the kidneys and liver.

It appears that what we are learning is that Vit D processing is one of many vital functions that interplay with many other vital processes.

Using the allopathic model of medicine we are not going to change the health at all, there needs to a board understanding and balance of the entire body system.

Synergy is occurring and compounding throughout our bodies Healthy or otherwise!

Vit D supplementing appears to change the expression of symptoms but not change the the disease itself.

What was it we are wanting to achieve by increasing Vit D intake?

Isn't the quest to see if there is QOL improvement by testing and increasing Vit D levels if there is a low reading, at the same time monitoring symptom changes.

And as Mark has mentioned some people will not be able to have testing done and he recommends supplementing as the option to see if symptoms 'change'.

;)
Nigel

as you know i think low d3 is, in part, a symptom of an underlying issue. similar to low uric acid. you can treat with inosine and ignore the underlying problem, or repair the broken system and have the low uric acid resolve incidentally. using zinc.. and the science has already been done, on that one at least.

NZer1 wrote:It appears that what we are learning is that Vit D processing is one of many vital functions that interplay with many other vital processes.

Everything in the human body is part of a system and therefore, change anywhere has systemic effects. And those effects have effects. This is simply what happens in any system. Everything is in some way inter-related to everything else.

Even more, there are relationships built on feedback loops designed to maintain balance, homeostasis, of virtually everything.

Using the allopathic model of medicine we are not going to change the health at all, there needs to a board understanding and balance of the entire body system.

I only study allopathic medicine and it is what is looking at all this complexity in greater and greater detail, peeling back the onion, blocking individual genes things to find out what is happening and it certainly is well aware that this is a system, not a bunch of discrete, unrelated parts.

I assume you are contrasting allopathic with some fuzzy marketing concept called "holistic" medicine.

My brother, as an example, practices allopathic medicine. He replaces clogged arteries with grafts, fixes broken heart valves.

He knows that would be much better if his patients ate right, exercised, didn't smoke or drink alcohol to excess, but sadly, when there is impaired blood flow to the heart and the patient is dying on the table, it is usually a little late to have those "holistic" conversations.

Synergy is occurring and compounding throughout our bodies Healthy or otherwise!

Yes, it is a system. All the parts are inter-related and when something is out of balance in one part, it usually has effects on other parts of the system and like a house of mirrors, those effects in turn have effects.

Vit D supplementing appears to change the expression of symptoms but not change the the disease itself.

I don't think that is at all true. What I was saying in earlier messages was simply that it is easier to prevent a problem caused by Vitamin D deficiency, than to repair the secondary damage caused by that deficiency which itself may need something other than vitamin D to initiate the repair.

I think a good example of why this is likely true. Vitamin D manages the repair of damaged blood vessels. If there is an uncorrected breech in the blood brain barrier because there is insufficient vitamin D to carry out the repair process quickly, then it sets off a process on the brain side that damages myelin. In MS, some degree of that damage is done by the time the disease becomes clinically manifest.

Vitamin D can fix the damaged blood vessel, but it may have no role in repairing damaged myelin. (It might have a role in meylin repair. It might also set up conditions for it to be repaired by something else. We simply don't know this yet.)

That doesn't mean that it wouldn't be a good idea to ensure an adequate vitamin D level because you have MS and vitamin D may not be able to fix everything that got broken as a result of that deficiency.

Hope that makes sense. Your statement sounds as though you are saying, forget it. The horse is already out of the barn.

I think a better analogy might be that the horse is out of the stall, but not the barn yet, so there is every reason to fix the barn door, in our case by maintaining adequate levels of vitamin D.

In theory when we figure out the right levels, it should ensure that any damage to the blood vessels is quickly repaired and that the immune response which it controls is properly managed limiting progression of the disease, at least to the extent that the "disease" is the breech of the blood brain barrier, not the secondary damage that occurs when it is breeched and things that shouldn't cross it do.

And even if it doesn't directly fix damaged myelin, by stopping further breeches in the BBB, it may well allow something else to get on with repairing the damage.

Hope that is clear.

What was it we are wanting to achieve by increasing Vit D intake?

To ensure that there is adequate vitamin D for it to deal with problems with the blood brain barrier and possibly aid in the repair of damage that has already occurred, if only by stopping further breeches of the BBB.

Putting on my "holistic" hat, you can't ignore diet, exercise, things like smoking and probably other things like bacterial infections, impaired blood flows and think that taking a vitamin D pill will magically make you healthy.

If, for example, the problem with the BBB is being caused by bacterial infection, vitamin D can repair the damage and certainly manages the immune response to infection of a cell, but you probably also need antibiotics. If there is constant turbulent blood flow causing the damage, then that probably has to be fixed too. Vitamin D is no more a magic cure-all than anything else. It is part of the solution, likely a critical part.

Isn't the quest to see if there is QOL improvement by testing and increasing Vit D levels if there is a low reading, at the same time monitoring symptom changes.

Absolutely. This is going to be the only way to find out exactly what role it plays in MS. What I would be testing, were I king, would be to see if I could measure changes first in active lesions which are supposed to be signs of a breakdown of the BBB. I would think that once you have adequate levels of vitamin D, these should be greatly diminished. They may not go away entirely with just vitamin D for the reason I note above. If there is a constant bacterial infection damaging the blood vessels, then that too has to be fixed. Or if you are smoking, drinking, not eating right and so on, all these things are going to play a role in the change in symptoms.

I would not expect someone who has an EDSS of 6.5 to magically have it go down, in the short run. I would in fact hope that adequate levels would have this effect in the long run, but as far as we know, vitamin D doesn't play a direct role in repairing damaged myelin which is probably what is the biggest contributor to the EDSS.

Looking at the midterm, I would think that you would have fewer relapses if you have adequate levels of vitamin D to the extent that vitamin D is able to stop further damage.

And as Mark has mentioned some people will not be able to have testing done and he recommends supplementing as the option to see if symptoms 'change'.

;)
Nigel

I think I would go further than Mark here. I think there is enough evidence that having adequate levels of vitamin D is important to many aspects of health that we would be well advised to maintain adequate levels whether we see short term progress or not. Cancers develop over many years and go undetected. We should be "treating" that all along by maintaining adequate vitamin D levels, not wait until we see blood or a bulging tumor.

Everyone can get testing done. There are a number of organizations that will send you a home test kit and you send back a piece of paper with some of your blood on it. There is a cost, but no reason anyone shouldn't get tested at some point.

jimmylegs wrote:as you know i think low d3 is, in part, a symptom of an underlying issue.

Let me take a wild guess at what that underlying issue is. Is it zinc? If I got it right, I might be tempted to play the PowerBall this week since I understand it now over $300 million.

I think it is a bit misleading to suggest that vitamin D deficiencies are the result of some mysterious, underlying issue.

There is no mystery at all that most people get inadequate amounts of exposure to UV-B radiation needed to make vitamin D, and there are few dietary sources of it that would offset this.

There are, of course, some number of people, who have genetic variations that impair their ability to metabolize vitamin D. These deficiencies occur in very high numbers among children who develop Type 1 diabetes, but have not been seen in some of the large scale genomic studies of pwMS so probably are only a few people with MS face this issue.

If you are taking vitamin D supplements or spending time getting UV-B exposure and your 25(OH)D level is not increasing, then you have a reason to investigate possible underlying problems.

For my money, based solely on your assertions, my first step in that case would be to check and correct my zinc level. That's a lot less expensive than getting a genetic test done. If that didn't work, the genetic testing might be in order.

But, I don't think we want anyone to think that this is any more complicated than ensuring adequate levels of supplementation or UV-B exposure as a starting point that is probably sufficient for the vast majority of people.

Should I play the PowerBall?

i covered off all that when i said 'in part'.

don't take my word for it, here's an intro re the zinc problem that affects a mere 30% of the population of the world... (a very low % estimate if 11.5umol/L is being used as the cut-off point...).
Zinc deficiency
http://www.who.int/publications/cra/cha ... 7-0280.pdf

good idea to get the zinc thing sorted out before bothering with the genetic testing...

Nutrigenomics: From Molecular Nutrition to Prevention of Disease (2006)
http://www.ncbi.nlm.nih.gov/pubmed/16567153
"Until recently, nutrition research concentrated on nutrient deficiencies and impairment of health. ... Nutritional genomics (nutrigenomics), the junction between health, diet, and genomics, can be seen as the combination of molecular nutrition and genomics. The diverse tissue and organ-specific effects of bioactive dietary components include gene-expression patterns (transcriptome); organization of the chromatin (epigenome); protein-expression patterns, including posttranslational modifications (proteome); as well as metabolite profiles (metabolome). Nutrigenomics will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phases of diet-related disease, and the extent to which individual sensitizing genotypes contribute to such diseases. Eventually, nutrigenomics will lead to evidence-based dietary intervention strategies for restoring health and fitness and for preventing diet-related disease. In this review, we provide a brief overview of nutrigenomics from our point of view by describing current strategies, future opportunities, and challenges."

Role of signalling systems in the effects of dietary factors on the expression of mammalian CYPs (2007)
http://informahealthcare.com/doi/abs/10 ... 55.3.2.185
"Changes in mammalian diets alter the hepatic expression of CYP drug-metabolising enzymes and endobiotic oxidases. Thus, dietary constituents may significantly influence the duration of action of chemicals in tissues. Recent improvements in the mechanistic information on the regulation of constitutive and inducible expression of CYPs has facilitated our understanding as to how dietary factors modulate expression. Altered regulation appears to occur either by direct activation of transcription factors or by indirect modulation of signal transduction pathways. For example, dietary lipid directly activates PPAR-α, or other nuclear hormone receptors, to elicit CYP induction, and vitamin A deficiency downregulates the growth hormone-responsive CYP2C11 by perturbing Janus kinase-signal transducers and activators of transcription signalling. This article focuses on the present understanding of the regulation of CYP genes by dietary nutrients."

very interesting stuff.

Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes (2011)
http://www.biomedcentral.com/1471-2164/12/95/
"The present studies have shown an increase in the mRNA of enzymes involved in the cholesterol biosynthesis pathway, implying that the sterol regulatory element binding proteins are more active in the liver and small intestine in lactating vs nonlactating rats. The data are consistent with a coordinated response to the overall increased energy demands of lactation and the specific needs of the pups for cholesterol so that there is adequate cholesterol for incorporation into milk and increased synthesis of bile acids; the latter in turn function to increase the intestinal absorption of cholesterol and lipids. We also demonstrated a marked increase in the expression of a key transporter important in the uptake of the essential element, zinc. Finally, we detected decreased mRNA from genes associated with T-cell signaling in the jejunum and ileum."

I've thrown this in to give some thought to the purpose of looking for reasons we are hi users of any mineral and or vitamin. It seems that we need to be aware of the other organisms and their needs as well.

The talk that 'MS is a Mimic of Lyme' may help understand why breaches of the BBB are enabling these diseases across into new territory. The CCSVI breaches maybe why the Lyme and CPn diseases antigens are now more prevalent in autopsy testing of Brain tissues.

Scientists reveal quirky feature of Lyme disease bacteria
posted on: march 21, 2013 - 8:00pm
Scientists have confirmed that the pathogen that causes Lyme Disease—unlike any other known organism—can exist without iron, a metal that all other life needs to make proteins and enzymes. Instead of iron, the bacteria substitute manganese to make an essential enzyme, thus eluding immune system defenses that protect the body by starving pathogens of iron.
To cause disease, Borrelia burgdorferi requires unusually high levels of manganese, scientists at Johns Hopkins University (JHU), Woods Hole Oceanographic Institution (WHOI), and the University of Texas reported. Their study, published March 22, 2013, in the Journal of Biological Chemistry, may explain some mysteries about why Lyme Disease is slow-growing and hard to detect and treat. The findings also open the door to search for new therapies to thwart the bacterium by targeting manganese.
"When we become infected with pathogens, from tuberculosis to yeast infections, the body has natural immunological responses," said Valeria Culotta, a molecular biologist at the JHU Bloomberg School of Public Health. The liver produces hepcidin, a hormone that inhibits iron from being absorbed in the gut and also prevents it from getting into the bloodstream. "We become anemic, which is one reason we feel terrible, but it effectively starves pathogens of iron they need to grow and survive," she said.
Borrelia, with no need for iron,has evolved to evade that defense mechanism. In 2000, groundbreaking research on Borrelia's genome by James Posey and Frank Gherardini at the University of Georgia showed that the bacterium has no genes that code to make iron-containing proteins and typically do not accumulate any detectable iron.
Culotta's lab at JHU investigates what she called "metal-trafficking" in organisms­—the biochemical mechanisms that cells and pathogens such as Borrelia use to acquire and manipulate metal ions for their biological purposes.
"If Borrelia doesn't use iron, what does it use?" Culotta asked.
To find out, Culotta's lab joined forces with Mak Saito, a marine chemist at WHOI, who had developed techniques to explore how marine life uses metals. Saito was particularly intrigued because of the high incidence of Lyme Disease on Cape Cod, where WHOI is located, and because he specializes in metalloproteins, which contain iron, zinc, cobalt, and other elements often seen in vitamin supplements. The metals serve as linchpins, binding to enzymes. They help determine the enzymes' distinctive three-dimensional shapes and the specific chemical reactions they catalyze.
Saito collaborated with biomedical researchers at Johns Hopkins University, applying his proteomic techniques to explore proteins in a terrestrial organism, the bacteria that cause Lyme Disease. Unlike all other known organisms, Borrelia burgdorferi need manganese (blue dot), rather than iron, to serve as linchpins bonded into key enzymes. The scientists found that to cause disease, Borrelia require unusually high levels of manganese. The findings open new avenues to search for ways to attack the bacteria.
(Photo Credit: Illustration by P. John Hart, University of Texas)
It's difficult to identify what metals are within proteins because typical analyses break apart proteins, often separating metal from protein. Saito used a liquid chromatography mass spectrometer to distinguish and measure separate individual Borrelia proteins according to their chemical properties and infinitesimal differences in their masses. Then he used an inductively coupled plasma mass spectrometer to detect and measure metals down to parts per trillion. Together, the combined analyses not only measured the amounts of metals and proteins, they showed that the metals are components of the proteins.
"The tools he has are fantastic," Culotta said. "Not too many people have this set of tools to detect metalloproteins."
The experiments revealed that instead of iron, Borrelia uses that element's next-door neighbor on the periodic chart, manganese, in certain Borrelia enzymes. These include an amino peptidase and an important antioxidant enzyme called superoxide dismutase.
Superoxide dismutase protects the pathogens against a second defense mechanism that the body throws against them. The body bombards pathogens with superoxide radicals, highly reactive molecules that cause damage within the pathogens. Superoxide dismutase is like an antioxidant that neutralizes the superoxides so that the pathogens can continue to grow.
The discoveries open new possibilities for therapies, Culotta said. "The only therapy for Lyme Disease right now are antibiotics like penicillin, which are effective if the disease is detected early enough. It works by attacking the bacteria's cell walls. But certain forms of Borrelia, such as the L-form, can be resistant because they are deficient in cell walls."
"So we'd like to find targets inside pathogenic cell that could thwart their growth," she continued. "The best targets are enzymes that the pathogens have, but people do not, so they would kill the pathogens but not harm people." Borrelia's distinctive manganese-containing enzymes such as superoxide dismutase may have such attributes.
In search of new avenues of attack, the groups are planning to expand their collaborative efforts by mapping out all the metal-binding proteins that Borellia uses and investigating biochemical mechanisms that the bacteria use to acquire manganese and directs it into essential enzymes. Knowing details of how that happens offers ways to disrupt the process and deter Lyme Disease.
Source: Woods Hole Oceanographic Institution
http://www.sciencecodex.com/scientists_ ... ria-109055

jimmylegs wrote:i covered off all that when i said 'in part'.

don't take my word for it, here's an intro re the zinc problem that affects a mere 30% of the population of the world... (a very low % estimate if 11.5umol/L is being used as the cut-off point...).
Zinc deficiency
http://www.who.int/publications/cra/cha ... 7-0280.pdf

I certainly won't take your word for it.

Did you read the study?

First, their method of estimating zinc deficiency, while the reasonable given the data limitations, is deeply flawed by the geography of what they found.

Zinc deficiency is estimated by surveys of commercial agriculture and food supply. That's fine in North America, but grossly underestimates food sources in the 3rd world where poverty forces people out of the market economy, but people in fact obtain relatively adequate levels of some foods from the chickens in the backyard, the fish from the nearby lake and so on.

But, more to the point, their study found that zinc deficiency is roughly equivalent to inadequate meat consumption. As such the areas of the world where this is a concern are places like Africa, the Eastern Mediterranean, and Southeast Asia.

If you read the study, you have to conclude that places where there is a high prevalence of zinc deficiency are the opposite of places where you have a high prevalence of MS, ie, North America and Europe.

The morbidity and mortality of concern in the study is not MS, but childhood diarrhea, pneumonia and malaria.

There may be an issue among strict vegetarians, but I don't think that is commonly linked to MS.

NZer1 wrote:Lyme Disease.
Source: Woods Hole Oceanographic Institution
http://www.sciencecodex.com/scientists_ ... ria-109055

Cool science to measure this.

An interesting and mostly unexplored aspect of vitamin D is that it mostly acts by expressing genes that create Ca++ transport receptors that allow Ca++ to be moved from one part of a cell to another or in and out of a cell through a membrane.

Not sure how this was discovered, but it always noted that these receptors can pass either Ca++ or Manganese++. No further explanation. Some hypotheses are that Mn++ could be a backup for times when there is no Ca++ available since an ionized atom will bind with any other atom willing to share an electron and be enough to set off a process such as cell replication.

Two other interesting points in this study: 1) oxidants play a key role in the immune response to infection which raises the question of why folks are so eager to take anti-oxidants, and 2) there are clearly situations where being deficient is not only a good thing, but there are natural processes available to create deficiencies to starve a pathogen that requires of some required element such as iron, as noted here.

From other reading on pathogens I see that their presence is not so much the issue it is the natural die off of their cells and how they transform to endo-toxins that is the issue for symptom creation.
If we are able to manage the volume of any bacteria or virus we are not physically aware of them, the straw that breaks the back is the endo-toxin load not being processed and broken down either soon enough or not at all and then if there are issues removing the volume of toxins they can collect and or also cycle around our system several times effecting our tissue and cells.

So interesting how anti-oxidants and also base minerals are the finer detail in the puzzle as you have pointed out Ed ;)

It's not what we know that is important!

Nigel

ABSTRACT

Glutathione (GSH), the most abundant intracellular low molecular weight thiol, has diverse physiological roles, and altered GSH status has been implicated in a number of chronic, acute, and age-related diseases, as well as the aging process itself. Its function as an antioxidant and determinant of cellular redox potential is crucial both for protection from reactive oxygen species as well as a signaling molecule involved in cellular proliferation, cell cycle regulation, and apoptosis. It is also an important thiol buffer, maintaining sulfhydryl groups in their reduced form, an additional mechanism for cellular signaling.

Whilst we are looking at base functions and the cellular needs another article has just come to hand to broaden the thoughts.

Glutathione has also emerged a key modulator of xenobiotic toxicity, most notably the persistent organic pollutants which are associated with many diseases of impaired metabolic activity, including diabetes, obesity, and cardiovascular disease. γ-glutamyl transpeptidase (GGT), an enzyme critical to the catabolism of GSH and its conjugates, appears to be an important biomarker for xenobiotic exposure, and for increased GSH demand. We review the physiological functions of glutathione, the limiting factors for its synthesis, as well as its clinical relevance, with particular emphasis on detoxification of environmental pollutants. We also review therapeutic approaches for enhancing GSH status.
http://restorativemedicine.org/journal/ ... relevance/


Nigel

yes sq, there are limitations to the study. that's why i noted limitations in the estimate if they're using the cutoff of 11.5 umol/L. all the other studies i've posted about zinc over the last 5 or 6 yrs are available in my regimens thread if you decide to read up in detail.

zinc helps elevate glutathione levels too by the way. research already posted elsewhere.

More neuros consider vit D, giving good background. Full paper www.ncbi.nlm.nih.gov/pmc/articles/PMC3582312
MarkW
PS Thanks Ed for your answers.

Ther Adv Neurol Disord. 2013 Mar;6(2):81-116. doi: 10.1177/1756285612473513.
Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis.
Pierrot-Deseilligny C, Souberbielle JC.
Source
Service de Neurologie 1, Hôpital de la Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie (Paris VI), Paris, France.
Abstract
The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.
KEYWORDS:
Epstein–Barr virus, genetics, multiple sclerosis, smoking, vitamin D
PMID: 23483715 [PubMed] PMCID: PMC3582312

Implementing Vitamin D guidance: call for evidence

Overview
NICE is issuing a call for evidence to support the development of public health guidance on ‘Vitamin D: implementation of existing guidance to prevent deficiency’. We are particularly interested in any relevant unpublished, commercial or other information that we would not be able to identify through a search of databases (for example, information about local interventions or processes to increase awareness and update of supplements containing vitamin D). This will help support consideration of the key questions in the scope for this work:
Question 1: How effective and cost effective are interventions to increase awareness and implementation of existing guidance on vitamin D among health professionals or others working with at-risk populations? What are the implications for professional training and practice?
Question 2: How effective and cost effective are interventions to increase awareness and uptake of existing guidance on vitamin D among at-risk groups (with special consideration given to those eligible for the Healthy Start scheme)?
Question 3: What helps or hinders the implementation of existing guidance on vitamin D by commissioners, providers, practitioners, those working with at-risk groups and people in at-risk groups?
Question 4: What local provision is made to ensure vitamin D supplements are available for different at-risk groups (including Healthy Start, prescriptions and over-the-counter sales)?
The closing date for submissions is the 30 April 2013.

Further details.